The worldwide distribution of HTLV infection, the mechanism of its transmission, and its role in various types of T-cell malignancies and patients with acquired immune deficiency syndrome (AIDS) and ARC has been extensively studied. A highly sensitive ELISA technique has been developed and extensively used for detection of HTLV infection. Seroepidemiological studies on the distribution of HTLV-III show that 95% of the AIDS and ARC patients and approximately 45% of healthy homosexuals carry HTLV-III antibodies. High incidence (65%) of HTLV-III antibodies has also been found in sera of Ugandan children collected in 1972. Detection of HTLV-III antibodies in sexual partners of AIDS and ARC cases in New York suggest heterosexual transmission of HTLV-III. Other seroepidemiological studies show that populations at risk for development of AIDS include Canadian and Japanese hemophiliacs, Haitian immigrants to New Guinea, Zairians, Rwandese, and male prostitutes in Singapore. The sera from AIDS and ARC patients has been shown to precipitate HTLV-III envelope proteins of 41,000; 120,000; and 160,000 daltons. HTLV-III inoculations into chimpanzees show that these animals seroconvert and virus has been reisolated from their peripheral blood indicating infection of these animals. None of these animals has so far developed AIDS-like syndrome. Increased prevalence of HTLV-I (9%) and HTLV-II (18%) antibodies have been observed among IV drug users who are also positive for HTLV-III (41%). The recombinant vaccinia virus induced envelope protein in mice was found to give an antibody response. These results are important in our efforts to produce a vaccine for AIDS.